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Biomedical subjects

L I Goldberg

Publications and source records attributed to L I Goldberg.

At least 19 recordsLinked to original sources
PubMed1991

Temperature is a powerful promoter of interleukin 2 transcription.

Elevated temperature has profound effects on the immune system, particularly by increasing T-cell proliferation rates, interleukin 1 (IL-1)-driven secretion of IL-2, and primary antibody responses to T-dependent antigens. Therefore, this study shows, in detail, the effects of incubation temperature (29 degrees C to 41 degrees C) on proliferation, IL-2 secretion, and IL-2 mRNA expression in both a murine thymoma cell line (EL4-6.1) and in nontransformed murine splenocytes. Temperature was found to be a positive regulator of IL-2 secretion whether or not IL-1 was part of the activation signal. Parallel effects were observed at the level of IL-2 gene expression. Messenger RNA was quantitated with a novel system, using solution hybridization followed by detection of RNA-DNA complexes by enzyme immunoassay. The time to onset of IL-2 mRNA expression was inversely related to temperature, and mRNA levels increased 20- to 50-fold with increases in average incubation temperature from 29 degrees C to 39 degrees C. This effect was observed whether cells were incubated at constant temperature or exposed intermittently to elevated temperature. Over the same intervals of time and temperature, mRNA levels for tau-actin and beta-tubulin remained relatively constant. Taken together, these findings suggest that temperature-mediated augmentation of IL-2 secretion does not require the presence of IL-1, and that the effect occurs at a pretranslational level.

Animals↗
PubMed1991

Effects of fenoldopam on renal blood flow and systemic hemodynamics during isoflurane anesthesia.

The authors compared the systemic hemodynamic and renal vascular effects of hypotension induced by fenoldopam with those produced by the most commonly used hypotensive agent, sodium nitroprusside, in 10 dogs. Mean arterial pressure decreased 26% +/- 3% from control following infusion with fenoldopam, and 30% +/- 2% following infusion with sodium nitroprusside (these decreases were not significantly different between the groups). Renal blood flow (RBF) was preserved during fenoldopam-induced hypotension (214 +/- 16 mL/min at baseline and 197 +/- 16 mL/min after fenoldopam-induced hypotension). In contrast, RBF decreased from 223 +/- 17 mL/min to 167 +/- 12 mL/min during sodium nitroprusside-induced hypotension (P less than 0.02). The differences in RBF between the two groups occurred in spite of the fact that cardiac output and pulmonary capillary wedge pressure were kept similar between the two groups. The authors conclude that fenoldopam, a selective dopamine1 (DA1) receptor agonist, preserves blood flow to the kidney during induced hypotension. On the other hand, sodium nitroprusside is a nonselective arteriolar and venous vasodilator that redistributes blood flow away from the kidneys during induced hypotension.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Effect of ring fluorination of epinephrine on its cardiovascular adrenoceptor activities.

Effects of fluorine (F) substitution on the 2- and 6-positions of the catechol ring of epinephrine (Epi) on its alpha- and beta-adrenoceptor agonist activities were studied in anesthetized dogs. Increments in heart rate and contractile force were used as measures of beta 1-adrenoceptor activity, while increases and decreases in blood pressure and decreases and increases in femoral blood flow were used as measures of alpha- and beta 2-adrenoceptor activities, respectively. F substitution on the 2- and 6-positions of the catechol ring yielded compounds with opposite receptor selectivities: 2-FEpi was a selective beta-adrenoceptor agonist with little agonist activity at alpha-adrenoceptors, while the 6-F analog was a selective a-adrenoceptor agonist with no significant beta-adrenoceptor effects. Of added significance, 2-FEpi was more potent than Epi as a beta 1-adrenoceptor agonist, while 6-F Epi was more potent than the parent compound as an alpha-adrenoceptor agonist. The possible mechanisms for the effects of ring fluorination on the adrenoceptor activities of Epi and other sympathomimetic amines are discussed.

Animals↗
PubMed1990

Preservation of renal blood flow during hypotension induced with fenoldopam in dogs.

The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine-1, (DA1) and dopamine-2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 +/- 8 per cent from control with infusion of fenoldopam (3.4 +/- 2.0 micrograms.kg-1.min-1) and 34 +/- 4 per cent with infusion of sodium nitroprusside (5.9 micrograms.kg-1.min-1) (NS). Renal blood flow (RBF) increased during fenoldopam-induced hypotension 11 +/- 7 per cent and decreased 21 +/- 8 per cent during sodium nitroprusside-induced hypotension (P less than 0.01). Sodium nitroprusside is a non-selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine-1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Histofluorescence techniques provide evidence for dopamine-containing neuronal elements in canine kidney.

Changes induced by hydrochloric acid in the excitation spectrum of catecholamine fluorophores associated with the innervation of the canine renal vasculature show that there are neuronal elements at the glomerular vascular poles containing predominantly dopamine. In contrast, the catecholamine fluorescence in the periadventitial layer of the arcuate arteries is derived from norepinephrine. The dopamine-containing structures may represent the prejunctional counterpart to the pharmacologically identified dopamine receptors in the renal vasculature. As such, this system may be involved in the normal regulation of renal blood flow and renin release.

Animals↗
PubMed1979

Dopamine vascular actions of N-substituted derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN).

N-ethyl, N-n-propyl, N-n-butyl, N,N-di-n-propyl and N-n-propyl-N-n-butyl derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) were screened for dopamine vascular agonist activity. Effects of intraarterial injections of the drugs on renal and femoral blood flow were measured in pentobarbital-anesthetized dogs before and after phenoxybenzamine (POB), 5--10 mg/kg. All DDTN derivatives were more potent vasoconstrictors than dopamine (DA) before POB. The di-substituted analogs were approximately 1/4 and the mono-substituted derivatives were about 1/16 as active as norepinephrine as vasoconstrictors. After POB the two di-substituted analogs were about 1/4 as active as DA in causing renal vasodilation. The three mono-substituted analogs produced relatively minor and inconsistent effects on renal blood flow, and were more than 100 times less effective than DA as vasodilators. The two di-substituted analogs markedly increased blood pressure with little effect on cardiac contractility in doses up to 32 micrograms/kg; whereas, the threshold dose of DA is 4--8 micrograms/kg. This and our previous results show that structure activity relationships of DA and ADTN, a semi-rigid analog of DA, are similar. However, the rigid analogs tend to be more potent vasoconstrictors than their flexible chain homologs.

Animals↗
PubMed1979

Vascular smooth muscle activity of 7-oxa-13-prostynoic acid.

The effects of 7-oxa-13-prostynoic acid (7-OPA), alone and as an antagonist of PGE2 and PGF2alpha, were investigaed in isolated rabbit aortic and canine renal arterial (diameter approximentaly 0.5 mm) strips. 7-OPA caused contractions in both preparations; threshold concentrations were 3- to 10-fold higher than the PGs and maximum contraction was 50-60%. In concentrations of 10(-5) M, 7-OPA inhibited contractions by PGF2alpha and PGE2. The same concentration of 7-OPA did not inhibit norepinephrine-induced contractions. These data indicate that 7-OPA is a partial agonist of PG receptors and produces its antagonism of PGE2 and PGF2alpha by that mechanism.

Animals↗
PubMed1978

Combined use of dopamine and prostaglandin A1 in patients with acute renal failure and hepatorenal syndrome.

Dopamine and prostaglandin A1 were infused intravenously in 4 patients with the hepatorenal syndrome, in 1 patient with acute tubular necrosis, and 1 patient with cortical necrosis. Large doses of prostaglandin A1 decreased arterial blood pressure preventing increase in dosage; in contrast, high doses of dopamine elevated blood pressure. When the two drugs were administered conjointly, much larger doses of each agent could be administered without change in arterial blood pressure. Significant improvement of renal function was not observed in any of these critically ill patients during or within 24 hours after dopamine and prostaglandin A1 administration. This study demonstrated that extremely large doses of these vasodilating agents can be safely administered conjointly.

Acute Kidney Injury↗
PubMed1978

N,N-Di-n-propyl dopamine: a qualitatively different dopamine vascular agonist.

N,N-di-n-propyl dopamine (DPDA) dilates the renal vascular bed by action on dopamine (DA) vascular receptors. In phenoxybenzamine-treated dogs DPDA caused dose-related increments in renal blood flow with an ED50 approximately 15 to 30 times greater than DA. The renal vasodilation was not antagonized by propranolol, antihistamines, atropine or hexamethonium, but was attenuated specifically by the DA antagonists metoclopramide and haloperidol. DPDA lacked beta adrenergic activity. In doses up to 480 microgram/kg i.v. DPDA had no effect on cardiac contractile force, whereas the minimal effective dose of DA is usually less than 8 microgram/kg. Increments in femoral or renal blood flow produced by DPDA were not antagonized by propranolol. DPDA and DA also differed in their effects on the femoral vascular bed. Before administration of phenoxybenzamine DPDA caused vasodilation while DA typically produced dose-related vasoconstriction. DPDA-induced femoral vasodilation was markedly attenuated by phenoxybenzamine and hexamethonium in contrast to renal vasodilation which was not affected by these drugs. DPDA was also a weaker vasoconstrictor than DA. These findings demonstrate that it is possible to synthesize DA vascular agonists with qualitatively different pharmacological profile than DA.

Animals↗